Nucleoporin

Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex.

Nuclear pores are large protein complexes that cross the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are about an average of 2000 nuclear pore complexes (NPCs), in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in the life cycle.

The proteins that make up the nuclear pore complex are known as nucleoporins. About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. Each NPC contains at least 456 individual protein molecules and is composed of 30 distinct proteins (nucleoporins).

The other half show structural characteristics typical of “natively unfolded” or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ordered secondary structure.

These disordered proteins are the FG nucleoporins, so-called because their amino-acid sequence contains many phenylalanine—glycine repeats.

1: Lavau CP, Aumann WK, Sze SK, Gupta V, Ripple K, Port SA, Kehlenbach RH, Wechsler DS. The SQSTM1-NUP214 fusion protein interacts with Crm1, activates Hoxa and Meis1 genes, and drives leukemogenesis in mice. PLoS One. 2020 Apr 28;15(4):e0232036. doi: 10.1371/journal.pone.0232036. PMID: 32343715; PMCID: PMC7188244.

2: Dewi FRP, Jiapaer S, Kobayashi A, Hazawa M, Ikliptikawati DK, Hartono, Sabit H, Nakada M, Wong RW. Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma. Autophagy. 2021 Apr;17(4):1001-1012. doi: 10.1080/15548627.2020.1741318. Epub 2020 Mar 24. PMID: 32207633; PMCID: PMC8078762.

3: Zhou J, Li G, Han G, Feng S, Liu Y, Chen J, Liu C, Zhao L, Jin F. Emodin induced necroptosis in the glioma cell line U251 via the TNF-α/RIP1/RIP3 pathway. Invest New Drugs. 2020 Feb;38(1):50-59. doi: 10.1007/s10637-019-00764-w. Epub 2019 Mar 28. PMID: 30924024; PMCID: PMC6985083.

4: Leveille E, Gonorazky HD, Rioux MF, Hazrati LN, Ruskey JA, Carnevale A, Spiegelman D, Dionne-Laporte A, Rouleau GA, Yoon G, Gan-Or Z. Triple A syndrome presenting as complicated hereditary spastic paraplegia. Mol Genet Genomic Med. 2018 Nov;6(6):1134-1139. doi: 10.1002/mgg3.492. Epub 2018 Oct 31. PMID: 30381913; PMCID: PMC6305671.

5: Lu B, Wang Z, Ding Y, Wang X, Lu S, Wang C, He C, Piao M, Chi G, Luo Y, Ge P. RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide. Cancer Lett. 2018 Jul 1;425:31-42. doi: 10.1016/j.canlet.2018.03.046. Epub 2018 Mar 30. PMID: 29608987.

6: Hazawa M, Lin DC, Kobayashi A, Jiang YY, Xu L, Dewi FRP, Mohamed MS, Hartono, Nakada M, Meguro-Horike M, Horike SI, Koeffler HP, Wong RW. ROCK-dependent phosphorylation of NUP62 regulates p63 nuclear transport and squamous cell carcinoma proliferation. EMBO Rep. 2018 Jan;19(1):73-88. doi: 10.15252/embr.201744523. Epub 2017 Dec 7. PMID: 29217659; PMCID: PMC5757218.

7: Lu B, Gong X, Wang ZQ, Ding Y, Wang C, Luo TF, Piao MH, Meng FK, Chi GF, Luo YN, Ge PF. Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation. Acta Pharmacol Sin. 2017 Nov;38(11):1543-1553. doi: 10.1038/aps.2017.112. Epub 2017 Aug 17. PMID: 28816233; PMCID: PMC5672068.

8: Cui C, Cui J, Jin F, Cui Y, Li R, Jiang X, Tian Y, Wang K, Jiang P, Gao J. Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury. Cell Physiol Biochem. 2017;42(5):1888-1896. doi: 10.1159/000479571. Epub 2017 Aug 3. PMID: 28772270.

9: Zhou Z, Lu B, Wang C, Wang Z, Luo T, Piao M, Meng F, Chi G, Luo Y, Ge P. RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species. Cancer Lett. 2017 Apr 1;390:77-90. doi: 10.1016/j.canlet.2017.01.004. Epub 2017 Jan 17. PMID: 28108311.

10: Liu JY, Reeves C, Diehl B, Coppola A, Al-Hajri A, Hoskote C, Mughairy SA, Tachrount M, Groves M, Michalak Z, Mills K, McEvoy AW, Miserocchi A, Sisodiya SM, Thom M. Early lipofuscin accumulation in frontal lobe epilepsy. Ann Neurol. 2016 Dec;80(6):882-895. doi: 10.1002/ana.24803. Epub 2016 Nov 26. PMID: 27766665.

11: Lu T, Bao Z, Wang Y, Yang L, Lu B, Yan K, Wang S, Wei H, Zhang Z, Cui G. Karyopherinβ1 regulates proliferation of human glioma cells via Wnt/β-catenin pathway. Biochem Biophys Res Commun. 2016 Sep 23;478(3):1189-97. doi: 10.1016/j.bbrc.2016.08.093. Epub 2016 Aug 24. PMID: 27568288.

12: Wang W, Wang WH, Azadzoi KM, Su N, Dai P, Sun J, Wang Q, Liang P, Zhang W, Lei X, Yan Z, Yang JH. Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis. Sci Rep. 2016 Mar 3;6:22550. doi: 10.1038/srep22550. PMID: 26935990; PMCID: PMC4776105.

13: Carvalhal S, Ribeiro SA, Arocena M, Kasciukovic T, Temme A, Koehler K, Huebner A, Griffis ER. The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation. Mol Biol Cell. 2015 Oct 1;26(19):3424-38. doi: 10.1091/mbc.E15-02-0113. Epub 2015 Aug 5. PMID: 26246606; PMCID: PMC4591688.

14: Huang C, Luo Y, Zhao J, Yang F, Zhao H, Fan W, Ge P. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS One. 2013 Jun 28;8(6):e66326. doi: 10.1371/journal.pone.0066326. PMID: 23840441; PMCID: PMC3695975.

15: Houlden H. The small, spastic, and furrowed tongue of Allgrove syndrome. Neurology. 2009 Apr 14;72(15):1366. doi: 10.1212/WNL.0b013e3181a0fe97. PMID: 19365062; PMCID: PMC2824517.

16: Karakoula K, Suarez-Merino B, Ward S, Phipps KP, Harkness W, Hayward R, Thompson D, Jacques TS, Harding B, Beck J, Thomas DG, Warr TJ. Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13. Genes Chromosomes Cancer. 2008 Nov;47(11):1005-22. doi: 10.1002/gcc.20607. PMID: 18663750.